rs1669617062

Variant names:

• chr1-223394368-T-C
• rs1669617062
• NM_152610.3:c.893T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152610.3(CCDC185):​c.893T>C​(p.Leu298Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,427,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCDC185 NM_152610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.724
• Publications: 0 publications found

Genes affected

CCDC185 (HGNC:26654): (coiled-coil domain containing 185)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC185	NM_152610.3	c.893T>C	p.Leu298Pro	missense_variant	Exon 1 of 1	ENST00000366875.5	NP_689823.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC185	ENST00000366875.5	c.893T>C	p.Leu298Pro	missense_variant	Exon 1 of 1	6	NM_152610.3	ENSP00000355840.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427790 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707346

African (AFR) AF: 0.00 AC: 0 AN: 32766

American (AMR) AF: 0.00 AC: 0 AN: 38672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25510

East Asian (EAS) AF: 0.00 AC: 0 AN: 37896

South Asian (SAS) AF: 0.00 AC: 0 AN: 82496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095304

Other (OTH) AF: 0.00 AC: 0 AN: 59178

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.893T>C (p.L298P) alteration is located in exon 1 (coding exon 1) of the CCDC185 gene. This alteration results from a T to C substitution at nucleotide position 893, causing the leucine (L) at amino acid position 298 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.72
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.098
Sift	Uncertain	0.016	D
Sift4G	Benign	0.092	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.25		Gain of glycosylation at L298 (P = 0.0382);
MVP		0.54
MPC		0.77
ClinPred		0.69	D
GERP RS		3.4
Varity_R		0.58
gMVP		0.29
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1669617062; hg19: chr1-223567710;